Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency.

Overconsumption of high-fat diets (HFDs) can critically affect synaptic and cognitive functions within telencephalic structures such as the medial prefrontal cortex (mPFC). The underlying mechanisms, however, remain largely unknown. Here we show that adolescence is a sensitive period for the emergence of prefrontal cognitive deficits in response to HFD. We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerability because (1) periadolescent HFD (pHFD) selectively downregulates prefrontal RELN+ cells and (2) augmenting mPFC RELN levels using transgenesis or prefrontal pharmacology prevents the pHFD-induced prefrontal cognitive deficits. We further identify N-methyl-d-aspartate-dependent long-term depression (NMDA-LTD) at prefrontal excitatory synapses as a synaptic signature of this association because pHFD abolishes NMDA-LTD, a function that is restored by RELN overexpression. We believe this study provides the first mechanistic insight into the vulnerability of the adolescent mPFC towards nutritional stress, such as HFDs. Our findings have primary relevance to obese individuals who are at an increased risk of developing neurological cognitive comorbidities, and may extend to multiple neuropsychiatric and neurological disorders in which RELN deficiency is a common feature.

European otorhinolaryngology training programs: results of a European survey about training satisfaction, work environment and conditions in six countries.

ORL-students and residents have an ongoing debate about the "best" programme in Europe. Aim of this study was to comparatively assess differences among programmes in training, satisfaction, quality of life (QoL) of residents and recent otorhinolaryngologist (ORL) specialists in France, Germany, Spain, Italy, Austria, and Belgium. A self-administered anonymous questionnaire, structured in ten sections including general information, provided guidance, working environment, training structure, teaching of medical students, publication work, QoL, and satisfaction with training, were emailed to residents and recent ORL specialists. 476 returned questionnaires from 6 countries revealed that daily work hours were the highest in France and Belgium with 11 and 10.4 h on average, respectively. QoL, work conditions, and salary were best in Germany followed by Austria in terms of possibility of part-time contracts, better respect for post-duty day off, and compensation for overtime. Satisfaction with training including support and guidance of seniors was lowest in Italy, but, on the other hand, the publication work and support had a more important place than in other countries. In Belgium, there was some gap between the quality of teaching and feedback from seniors as well as apprenticeship. The highest satisfaction with training was in France and Spain followed by Austria. The study results provide guidance before choosing an ORL training programme in Europe. Country-specific strengths could be included into future harmonization efforts to improve all programmes, facilitate professional exchange and, finally, establish standards-of-care carried out by well-trained doctors also looking after a satisfying work-life balance.

[Elastography as an additional tool in breast sonography. Technical principles and clinical applications]. / Elastographie als Zusatzmodalität der Mammasonographie. Technische Grundlagen und klinische Anwendungsmöglichkeiten.

In recent years the use of elastography in addition to sonography has become a routine clinical tool for the characterization of breast masses. Whereas free hand compression elastography results in qualitative imaging of tissue stiffness due to induced compression, shear wave elastography displays quantitative information of tissue displacement. Recent studies have investigated the use of elastography in addition to sonography and improvement of specificity in differentiating benign from malignant breast masses could be shown. Therefore, additional use of elastography could help to reduce the number of unnecessary biopsies in benign breast lesions especially in category IV lesions of the ultrasound breast imaging reporting data system (US-BI-RADS).

[Acute jaw-thoracic pain and syncope in a 41-year-old man]. / Akuter Kiefer-Thorax-Schmerz und Synkope bei einem 41-jährigen Patienten.

A 41-year-old physically active man with no significant past medical history presented with sudden thoracic pain. The patient was referred to the next tertiary care hospital. A CT scan showed an ectasia of the ascending aorta with irregularities of the aortic wall without dissection. Despite initial refusal, the patient was referred to a university hospital with experience in aortic surgery. A triphase ECG-synchronized cardiothoracic flash protocol performed on a 256 line CT scanner confirmed an aortic intramural hematoma and a covered aortic perforation. Shortly afterwards the patient collapsed and had to be resuscitated.

Perineuronal net structure as a non-cellular mechanism contributing to affective state: A scoping review.

Affective state encompasses emotional responses to our physiology and influences how we perceive and respond within our environment. In affective disorders such as depression, cognitive adaptability is challenged, and structural and functional brain changes have been identified. However, an incomplete understanding persists of the molecular and cellular mechanisms at play in affective state. An exciting area of newly appreciated importance is perineuronal nets (PNNs); a specialised component of extracellular matrix playing a critical role in neuroprotection and synaptic plasticity. A scoping review found 24 studies demonstrating that PNNs are still a developing field of research with a promising general trend for stress in adulthood to increase the intensity of PNNs, whereas stress in adolescence reduced (potentially developmentally delayed) PNN numbers and intensity, while antidepressants correlated with reduced PNN numbers. Despite promising trends, limited research underscores the need for further exploration, emphasizing behavioral outcomes for validating affective states. Understanding PNNs' role may offer therapeutic insights for depression and inform biomarker development, advancing precision medicine and enhancing well-being.

Transgenic expression of the FTDP-17 tauV337M mutation in brain dissociates components of executive function in mice.

Frontotemporal lobe dementia (FTD) is a heterogeneous range of disorders, a subset of which arise from fully penetrant, autosomal dominant point mutations in the gene coding for the microtubule associated protein tau. These genetic tauopathies are associated with complex behavioural/cognitive disturbances, including compromised executive function. In the present study, we modelled the effects of the FTD with Parkinsonism linked to chromosome 17 (FTDP-17) tauV337M mutation (known as the Seattle Family A mutation) expressed in mice on executive processes using a novel murine analogue of the Stroop task. Employing biconditional discrimination procedures, Experiment 1 showed that normal mice, but not mice with excitotoxic lesions of the medial prefrontal cortex, were able to use context cues to resolve response conflict generated by incongruent stimulus compounds. In contrast to predictions, response conflict resolution was not disrupted by the tauV337M mutation (Experiment 2). However, while context appropriate actions were goal-directed in wild-type mice, performance of tauV337M mice was not goal-directed (Experiment 3). The results indicate that the tauV337M mutation in mice disrupts, selectively, a subset of processes related to executive function.

MRI-based breast volumetry-evaluation of three different software solutions.

As lipofilling of the female breast is becoming more popular in plastic surgery, the use of MRI to assess breast volume has been employed to control postoperative results. Therefore, we sought to evaluate the accuracy of magnetic resonance imaging (MRI)-based breast volumetry software tools by comparing the measurements of silicone implant augmented breasts with the actual implant volume specified by the manufacturer. MRI-based volume analysis was performed in eight bilaterally augmented patients (46 ± 9 years) with three different software programs (Brainlab© I plan 2.6 neuronavigation software; mass analysis, version 5.3, Medis©; and OsiriX© v.3.0.2. 32-bit). The implant volumes analysed by the BrainLab© software had a mean deviation of 2.2 ± 1.7% (r = 0.99) relative to the implanted prosthesis. OsiriX© software analysis resulted in a mean deviation of 2.8 ± 3.0% (r = 0.99) and the Medis© software had a mean deviation of 3.1 ± 3.0% (r = 0.99). Overall, the volumes of all analysed breast implants correlated very well with the real implant volumes. Processing time was 10 min per breast with each system and 30 s (OsiriX©) to 5 min (BrainLab© and Medis©) per silicone implant. MRI-based volumetry is a powerful tool to calculate both native breast and silicone implant volume in situ. All software solutions performed well and the measurements were close to the actual implant sizes. The use of MRI breast volumetry may be helpful in: (1) planning reconstructive and aesthetic surgery of asymmetric breasts, (2) calculating implant size in patients with missing documentation of a previously implanted device and (3) assessing post-operative results objectively.

[Novel surgical techniques for treatment of benign prostatic hyperplasia]. / Neue operative Techniken zur Therapie des benignen Prostatasyndroms.

In recent years new surgical techniques to treat benign prostatic hyperplasia have been introduced into urological practice and evaluated in clinical studies. Complications of standard procedures, e.g. transurethral resection of the prostate (TURP), can be avoided while maintaining equivalent clinical outcomes. The main goal is preservation of erectile and ejaculatory function. Furthermore, outpatient treatment associated with a rapid patient recovery would be desirable. This article presents the course of the interventions, the mechanisms of action and current clinical evidence for novel mechanical approaches of recanalization, water-based ablation as well as prostate artery embolization. Initial study results partially indicate that in the future practically all patients can be offered an individualized surgical technique, which provides optimal symptomatic and functional improvements with a minimized risk of complications.

Dietary influences on cognition.

Obesity is a world-wide crisis with profound healthcare and socio-economic implications and it is now clear that the central nervous system (CNS) is a target for the complications of metabolic disorders like obesity. In addition to decreases in physical activity and sedentary lifestyles, diet is proposed to be an important contributor to the etiology and progression of obesity. Unfortunately, there are gaps in our knowledge base related to how dietary choices impact the structural and functional integrity of the CNS. For example, while chronic consumption of hypercaloric diets (increased sugars and fat) contribute to increases in body weight and adiposity characteristic of metabolic disorders, the mechanistic basis for neurocognitive deficits in obesity remains to be determined. In addition, studies indicate that acute consumption of hypercaloric diets impairs performance in a wide variety of cognitive domains, even in normal non-obese control subjects. These results from the clinical and basic science literature indicate that diet can have rapid, as well as long lasting effects on cognitive function. This review summarizes our symposium at the 2017 Society for the Study of Ingestive Behavior (SSIB) meeting that discussed these effects of diet on cognition. Collectively, this review highlights the need for integrated and comprehensive approaches to more fully determine how diet impacts behavior and cognition under physiological conditions and in metabolic disorders like type 2 diabetes mellitus (T2DM) and obesity.

Weight gain adequacy and pregnancy outcomes in gestational diabetes: a meta-analysis.

The Institute of Medicine updated guidelines for gestational weight gain in 2009, with no special recommendations for gestational diabetes. Our objectives were to describe the prevalence of weight gain adequacy and their association with adverse pregnancy outcomes in gestational diabetes. We searched MEDLINE, EMBASE, COCHRANE and SCOPUS. We calculated the pooled prevalence of gain adequacy and relative risks for pregnancy outcomes within Institute of Medicine categories. Thirty-three studies/abstracts (88,599 women) were included. Thirty-one studies provided data on the prevalence of weight gain adequacy; it was adequate in 34% (95% CI: 29-39%) of women, insufficient in 30% (95% CI: 27-34%) and excessive in 37% (95% CI: 33-41%). Excessive gain was associated with increased risks of pharmacological treatment, hypertensive disorders of pregnancy, caesarean section, large for gestational age and macrosomic babies, compared to adequate or non-excessive gain. Weight gain below the guidance had a protective effect on large babies (RR: 0.71; 95% CI: 0.56-0.90) and macrosomia (RR 0.57; 95% CI 0.40-0.83), and did not increase the risk of small babies (RR 1.40; 95% CI 0.86-2.27). Less than recommended weight gain would be beneficial, while effective prevention of excessive gain is of utmost importance, in gestational diabetes pregnancies. Nevertheless, no ideal range for weight gain could be established.

Waist circumference and waist-to-hip ratio are related to gestational glucose tolerance.

OBJECTIVE: To evaluate the relationship of central fat distribution with gestational glucose tolerance during the usual time for screening gestational diabetes. RESEARCH DESIGN AND METHODS: This cross-sectional study investigated 1,113 consecutive women, > or = 20 years old, pregnant for approximately 21 to 28 weeks, without history of previous diabetes outside pregnancy, who attended two general prenatal care units in Porto Alegre, Brazil, from 1991 to 1993. Weight, height, waist and hip circumferences, and skinfolds were measured, and a 2-h, 75-g glucose tolerance test was performed. Data were analyzed using multiple linear regression models. RESULTS: Waist-to-hip ratio (WHR) and waist circumference were independently associated with higher 2-h glycemia. Glycemic level was 0.11 and 0.13 mmol/l greater for each standard deviation increase in WHR (0.06) and waist circumference (8.0 cm), respectively (P < 0.02). Restricting analyses to the subset of women with uterine height < or = 26 cm improved the association (0.13 and 0.19 mmol/l, respectively, P < 0.02); differences of 0.22 and 0.19 mmol/l were observed for 1 SD changes in the sum of skinfold thicknesses (24.7 mm) and in age (5.5 years), respectively. CONCLUSIONS: Central fat distribution measured in pregnancy is an independent predictor of gestational glucose intolerance. This finding supports the concept that NIDDM and gestational diabetes are parts of the same disease, differing basically in their moment of detection. The usefulness of these anthropometric measurements in identifying pregnant women at high risk of having gestational glucose intolerance merits further investigation.

Fasting plasma glucose is a useful test for the detection of gestational diabetes. Brazilian Study of Gestational Diabetes (EBDG) Working Group.

OBJECTIVE: To evaluate fasting plasma glucose as a screening test for states of gestational diabetes. RESEARCH DESIGN AND METHODS: Baseline data of a cohort conducted in general prenatal care units in Brazil, enrolling 5,579 women aged > or = 20 years with gestational ages of 24-28 weeks at the time of testing and no previous diagnosis of diabetes. A standardized 2-h 75-g oral glucose tolerance test was performed in 5,010 women. Gestational diabetes and its subcategories--diabetes and impaired glucose tolerance--were defined according to the 1994 World Health Organization panel recommendations. We evaluated screening properties of calculated sensitivity and specificity for fasting plasma glucose with receiver operator characteristic curves. RESULTS: For detection of the subcategory diabetes, a fasting plasma glucose of 89 mg/dl jointly maximizes sensitivity (88%) and specificity (78%), identifying 22% of the women as test-positive. For detection of impaired glucose tolerance, a value of 85 mg/dl jointly maximizes sensitivity and specificity (68%), identifying as test-positive 35% of the women. Lowering the cut point to 81 mg/dl increases sensitivity to 81%, but decreases specificity to 54%, labeling as test-positive 49% of the women. CONCLUSIONS: Fasting plasma glucose is a useful test for the screening of both subcategories of gestational diabetes, a threshold of 85 mg/dl being an acceptable option. Effective screening for the subcategory diabetes can be achieved using a cut point of 89 mg/dl. If greater emphasis is placed on the detection of impaired glucose tolerance, a lower value, 81 mg/dl, may be needed.

Gestational diabetes mellitus diagnosed with a 2-h 75-g oral glucose tolerance test and adverse pregnancy outcomes.

OBJECTIVE: To evaluate American Diabetes Association (ADA) and World Health Organization (WHO) diagnostic criteria for gestational diabetes mellitus (GDM) against pregnancy outcomes. RESEARCH DESIGN AND METHODS: This cohort study consecutively enrolled Brazilian adult women attending general prenatal clinics. All women were requested to undertake a standardized 2-h 75-g oral glucose tolerance test (OGTT) between their estimated 24th and 28th gestational weeks and were then followed to delivery. New ADA criteria for GDM require two plasma glucose values > or = 5.3 mmol/l (fasting), > or = 10 mmol/l (1 h), and > or = 8.6 mmol/l (2 h). WHO criteria require a plasma glucose > or = 7.0 mmol/l (fasting) or > or = 7.8 mmol/l (2 h). Individuals with hyperglycemia indicative of diabetes outside of pregnancy were excluded. RESULTS: Among the 4,977 women studied, 2.4% (95% CI 2.0-2.9) presented with GDM by ADA criteria and 7.2% (6.5-7.9) by WHO criteria. After adjustment for the effects of age, obesity, and other risk factors, GDM by ADA criteria predicted an increased risk of macrosomia (RR 1.29, 95% CI 0.73-2.18), preeclampsia (2.28, 1.22-4.16), and perinatal death (3.10, 1.42-6.47). Similarly, GDM by WHO criteria predicted increased risk for macrosomia (1.45, 1.06-1.95), preeclampsia (1.94, 1.22-3.03), and perinatal death (1.59, 0.86-2.90). Of women positive by WHO criteria, 260 (73%) were negative by ADA criteria. Conversely, 22 (18%) women positive by ADA criteria were negative by WHO criteria. CONCLUSIONS: GDM based on a 2-h 75-g OGTT defined by either WHO or ADA criteria predicts adverse pregnancy outcomes.

Integration of reward signalling and appetite regulating peptide systems in the control of food-cue responses.

Understanding the neurobiological substrates that encode learning about food-associated cues and how those signals are modulated is of great clinical importance especially in light of the worldwide obesity problem. Inappropriate or maladaptive responses to food-associated cues can promote over-consumption, leading to excessive energy intake and weight gain. Chronic exposure to foods rich in fat and sugar alters the reinforcing value of foods and weakens inhibitory neural control, triggering learned, but maladaptive, associations between environmental cues and food rewards. Thus, responses to food-associated cues can promote cravings and food-seeking by activating mesocorticolimbic dopamine neurocircuitry, and exert physiological effects including salivation. These responses may be analogous to the cravings experienced by abstaining drug addicts that can trigger relapse into drug self-administration. Preventing cue-triggered eating may therefore reduce the over-consumption seen in obesity and binge-eating disorder. In this review we discuss recent research examining how cues associated with palatable foods can promote reward-based feeding behaviours and the potential involvement of appetite-regulating peptides including leptin, ghrelin, orexin and melanin concentrating hormone. These peptide signals interface with mesolimbic dopaminergic regions including the ventral tegmental area to modulate reactivity to cues associated with palatable foods. Thus, a novel target for anti-obesity therapeutics is to reduce non-homeostatic, reward driven eating behaviour, which can be triggered by environmental cues associated with highly palatable, fat and sugar rich foods.

Treatment of osteopenia and osteoporosis after kidney transplantation.

BACKGROUND: Osteopenia and osteoporosis are frequent complications after kidney transplantation. Data for the treatment of low bone mass after kidney transplantation are not available. METHODS: To test the efficacy of antiresorptive treatment, 46 patients with osteopenia or osteoporosis after kidney transplantation (bone mineral density < or =1.5 SD below normal) were randomly assigned to three groups cyclically treated as follows: group 1 with daily oral clodronate (800 mg) and group 2 with daily intranasal calcitonin (200 IU) for 2 weeks every 3 months. These two groups were compared with a control group (group 3). Every patient was supplemented with 500 mg of calcium per day. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DEXA) at the lumbar spine and femoral neck before and after the 12-month treatment period. RESULTS: BMD at the lumbar spine was increased by 4.6% in the clodronate group (n=15, P=0.005), by 3.2% in the calcitonin group (n=16, P=0.034), and by 1.8% in the control group (n=15, P=0.265). However, the differences in BMD changes among the groups were not statistically significant. During therapy, serum calcium decreased slightly in all groups by 4.6%; however, parathyroid hormone values increased significantly in the treatment groups by 116%. Therapy was well tolerated without impact on graft function. CONCLUSIONS: Cyclical therapy with clodronate or calcitonin appears to induce a gain in BMD at the lumbar spine in patients with low bone mass after kidney transplantation. This treatment had no adverse impact on graft function but may aggravate preexisting secondary hyperparathyroidism.

Indirect MR arthrography of the unexercised glenohumeral joint in patients with rotator cuff tears.

RATIONALE AND OBJECTIVES: To evaluate the diagnostic utility of indirect MR arthrography of the unexercised glenohumeral joint in patients with rotator cuff tears confirmed by arthroscopy or arthrotomy as the gold standard. METHODS: Twenty-six patients underwent conventional MR imaging and indirect MR arthrography of the stationary glenohumeral joint using a wrap-around surface coil. Unenhanced T1-weighted spin echo/T2-weighted fast spin echo sequences and T1-weighted gradient echo sequences, adding spectral fat suppression after intravenous administration of contrast medium, were performed in the oblique coronal and oblique sagittal planes. Images were analyzed by three experienced radiologists in consensus. Levels of diagnostic confidence were evaluated using a four-point scale of diagnostic certainty. RESULTS: Performing indirect MR arthrography of the unexercised shoulder leads to a diagnostically efficient enhancement of joint fluid (120% at 4 minutes and 145% at 8 minutes after intravenous injection of gadodiamide). In terms of soft tissue delineation, characterization of rotator cuff tears was significantly improved by using enhanced fat-suppressed T1-weighted gradient echo sequences compared with conventional MR imaging. CONCLUSIONS: Indirect MR arthrography without glenohumeral joint exercise in the diagnosis of rotator cuff tears is feasible and represents a more convenient and less time-consuming alternative to indirect MR arthrography after joint exercise.

Conservative management of pyogenic osteomyelitis of the occipitocervical junction.

STUDY DESIGN: A report of three cases of pyogenic osteomyelitis of the occipitocervical junction. OBJECTIVE: To describe the conservative management of pyogenic osteomyelitis of the occipitocervical junction. SUMMARY OF BACKGROUND DATA: The therapeutic approach to inflammation of the upper cervical spine is controversial. METHODS: Pyogenic osteomyelitis of the occipitocervical junction is rare. In the orthopedic literature, only a few case reports with variable treatment methods are available. Three patients with pyogenic osteomyelitis of the occipitocervical junction were treated nonoperatively. Intravenous antibiotic therapy was begun after direct cultures or blood cultures were obtained. Early mobilization was accomplished by application of a halo vest. RESULTS: Two patients recovered by spontaneous fusion of the occipitocervical junction. Instability developed in the spine of one patient, but she refused further treatment. CONCLUSIONS: Diagnosis of osteomyelitis of the upper cervical spine is difficult. In cases with absence of neurologic symptoms or spinal abscess formation, treatment can be nonoperative.